Post-Operative Pain
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of the sublingual Sufentanil Tablet (ST) 30 mcg to the sublingual Placebo Tablet (PT) for the short-term management of moderate-to-severe acute post-operative pain in patients after abdominal surgery.
Interventions
DRUGSufentanil Tablet 30 mcg
DRUGPlacebo Tablet
Sponsors
Talphera, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(additional criteria not specified here): 1. Patients who are scheduled to undergo one of the following procedures with general anesthesia or spinal anesthesia that does not include intrathecal opioids during the operation: * abdominoplasty * open tension-free inguinal hernioplasty (Lichenstein repair with mesh) * laparoscopic abdominal surgery 2. Patients classified as American Society of Anesthesiologists (ASA) class I - III (Appendix I). 3. Female patients of childbearing potential must be using an effective method of birth control at the time of screening visit 4. Patients who are expected to have moderate-to-severe post-operative pain for at least 24 hours.
Exclusion criteria
(additional criteria not specified here): 1. Patients who have taken an opioid for more than 30 consecutive days, at a daily dose of more than 15 mg of morphine (or equivalent), within the past 3 months prior to surgery 2. Patients who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days of the first dose of study drug. 3. Patients with current sleep apnea that has been documented by a sleep laboratory study or are on home continuous positive airway pressure (CPAP). 4. Patients who previously have had abdominoplasty or have had an inguinal hernia repair on the same side.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Summed Pain Intensity Difference (SPID) Over the 12-hour Study Period (SPID12). | 12 hours | The primary outcome measure is the summed pain intensity difference to baseline over the 12-hour study period (SPID-12). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 12 hour study period. The SPID-12 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The observed SPID-12 scores ranged from -42.15 to 71.87 in the active group and -34.96 to 64.37 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TOTPAR12 | 12 hours | Total pain relief over the 12 hours. The observed total pain relief scores ranged from 4.08 to 47.50 in the active group and 1.77 to 33.71 in the placebo group. A higher score indicates greater pain relief. |
| TOTPAR24 | 24 Hours | Total pain relief over the 24 hour study period. The observed total pain relief scores ranged from 12.35 to 95.23 in the active group and 2.61 to 82.04 in the placebo group. A higher score indicates greater pain relief. |
| Time-weighted SPRID12 | 12 hours | Time-weighted summed pain relief intensity difference (SPRID) over the 12 hour study period. The observed SPRID scores ranged from -38.08 to 106.82 in the active group and -20.10 to 95.72 in the placebo group. A negative score indicates an increase in pain intensity and decrease in pain relief, while a higher score indicates a greater decrease in pain intensity and increase in pain relief. |
| Time-weighted SPRID24 | 24 hours | Time-weighted summed pain relief intensity difference (SPRID) over the 24 hour study period. The observed SPRID scores ranged from -49.67 to 222.04 in the active group and -24.97 to 237.54 in the placebo group. A negative score indicates an increase in pain intensity and decrease in pain relief, while a higher score indicates a greater decrease in pain intensity and increase in pain relief. |
| Patient Global Assessment | 24 hours | Proportion of patients who responded good or excellent to the global assessment of method of pain control at 24 hours |
| Time-weighted Summed Pain Intensity Difference (SPID) Over the 24-hour Study Period (SPID24). | 24 hours | The primary outcome measure is the summed pain intensity difference to baseline over the 24-hour study period (SPID-24). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 24 hour study period. The SPID-24 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The observed SPID-24 scores ranged from -70.00 to 148.70 in the active group to -58.09 to 160.24 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity. |
| Summed Pain Intensity Difference | 1 hour | The SPID-1 is calculated by summing the difference to baseline between baseline pain score and the pain score at each assessment time point through 1 hour. The observed SPID scores ranged from -2.00 to 5.25 in the active group to -4.90 to 3.00 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity. |
| Analysis of Total Number of Doses Used During the 12-Hour Study Period in the ITT Population | Cumulative through 12 hours | — |
| Analysis of Total Number of Doses Used During the 24-Hour Study Period in the ITT Population | 24 hours | — |
| Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | Cumulative through 6 hours | — |
| Healthcare Professional Global Assessment | 24 hours | Proportion of Health Care Professionals who responded good or excellent to the global assessment of method of pain control at 24 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sufentanil Tablet 30 mcg A stratified randomization will be applied in this study with sex as a stratification factor. Patients who meet all inclusion and none of the exclusion criteria at screening, and following surgery, will be randomly assigned at a 2:1 ratio to treatment with ST 30 mcg or PT within one of two groups (male or female) at each study center. Patients may receive a dose of study medication no more frequently than once per hour. The study may last up to 48 hours.
Sufentanil Tablet 30 mcg | 107 |
| Placebo Tablet A stratified randomization will be applied in this study with sex as a stratification factor. Patients who meet all inclusion and none of the exclusion criteria at screening, and following surgery, will be randomly assigned at a 2:1 ratio to treatment with ST 30 mcg or PT within one of two groups (male or female) at each study center. Patients may receive a dose of study medication no more frequently than once per hour. The study may last up to 48 hours.
Placebo Tablet | 54 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 4 | 10 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sufentanil Tablet 30 mcg | Placebo Tablet | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 53 Participants | 159 Participants |
| Gender Female | 73 Participants | 36 Participants | 109 Participants |
| Gender Male | 34 Participants | 18 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 107 | 21 / 54 |
| serious Total, serious adverse events | 0 / 107 | 2 / 54 |
Outcome results
Primary
Time-weighted Summed Pain Intensity Difference (SPID) Over the 12-hour Study Period (SPID12).
The primary outcome measure is the summed pain intensity difference to baseline over the 12-hour study period (SPID-12). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 12 hour study period. The SPID-12 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The observed SPID-12 scores ranged from -42.15 to 71.87 in the active group and -34.96 to 64.37 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity.
Time frame: 12 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Time-weighted Summed Pain Intensity Difference (SPID) Over the 12-hour Study Period (SPID12). | 25.84 units on a scale | Standard Error 1.71 |
| Placebo Tablet | Time-weighted Summed Pain Intensity Difference (SPID) Over the 12-hour Study Period (SPID12). | 13.14 units on a scale | Standard Error 2.35 |
Secondary
Analysis of Total Number of Doses Used During the 12-Hour Study Period in the ITT Population
Time frame: Cumulative through 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Analysis of Total Number of Doses Used During the 12-Hour Study Period in the ITT Population | 4.4 mean number of tablets taken | Standard Deviation 2 |
| Placebo Tablet | Analysis of Total Number of Doses Used During the 12-Hour Study Period in the ITT Population | 4.7 mean number of tablets taken | Standard Deviation 2.3 |
Secondary
Analysis of Total Number of Doses Used During the 24-Hour Study Period in the ITT Population
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Analysis of Total Number of Doses Used During the 24-Hour Study Period in the ITT Population | 7.09 mean number of tablets taken | Standard Deviation 3.6 |
| Placebo Tablet | Analysis of Total Number of Doses Used During the 24-Hour Study Period in the ITT Population | 6.40 mean number of tablets taken | Standard Deviation 3.8 |
Secondary
Healthcare Professional Global Assessment
Proportion of Health Care Professionals who responded good or excellent to the global assessment of method of pain control at 24 hours
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sufentanil Tablet 30 mcg | Healthcare Professional Global Assessment | 80.4 Percentage of HCPs |
| Placebo Tablet | Healthcare Professional Global Assessment | 53.7 Percentage of HCPs |
Secondary
Patient Global Assessment
Proportion of patients who responded good or excellent to the global assessment of method of pain control at 24 hours
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sufentanil Tablet 30 mcg | Patient Global Assessment | 80.4 Percentage of patients |
| Placebo Tablet | Patient Global Assessment | 51.9 Percentage of patients |
Secondary
Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population
Time frame: Cumulative through 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 0.5 mean number of doses used | Standard Deviation 1.4 |
| Placebo Tablet | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 2.1 mean number of doses used | Standard Deviation 2.9 |
Secondary
Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population
Time frame: Cumulative through 6 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 0.3 mean number of doses used | Standard Deviation 0.7 |
| Placebo Tablet | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 1.1 mean number of doses used | Standard Deviation 1.1 |
Secondary
Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population
Time frame: Cumulative through 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 0.4 mean number of doses used | Standard Deviation 1 |
| Placebo Tablet | Summary of Number of Rescue Morphine Doses Used by Study Period in the ITT Population | 1.6 mean number of doses used | Standard Deviation 1.8 |
Secondary
Summed Pain Intensity Difference
The SPID-1 is calculated by summing the difference to baseline between baseline pain score and the pain score at each assessment time point through 1 hour. The observed SPID scores ranged from -2.00 to 5.25 in the active group to -4.90 to 3.00 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity.
Time frame: 1 hour
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Summed Pain Intensity Difference | 1.09 units on a scale | Standard Error 0.15 |
| Placebo Tablet | Summed Pain Intensity Difference | -0.37 units on a scale | Standard Error 0.21 |
Secondary
Time-weighted SPRID12
Time-weighted summed pain relief intensity difference (SPRID) over the 12 hour study period. The observed SPRID scores ranged from -38.08 to 106.82 in the active group and -20.10 to 95.72 in the placebo group. A negative score indicates an increase in pain intensity and decrease in pain relief, while a higher score indicates a greater decrease in pain intensity and increase in pain relief.
Time frame: 12 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Time-weighted SPRID12 | 47.03 units on a scale | Standard Error 2.35 |
| Placebo Tablet | Time-weighted SPRID12 | 28.62 units on a scale | Standard Error 3.24 |
Secondary
Time-weighted SPRID24
Time-weighted summed pain relief intensity difference (SPRID) over the 24 hour study period. The observed SPRID scores ranged from -49.67 to 222.04 in the active group and -24.97 to 237.54 in the placebo group. A negative score indicates an increase in pain intensity and decrease in pain relief, while a higher score indicates a greater decrease in pain intensity and increase in pain relief.
Time frame: 24 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Time-weighted SPRID24 | 103.88 units on a scale | Standard Error 4.81 |
| Placebo Tablet | Time-weighted SPRID24 | 73.05 units on a scale | Standard Error 6.62 |
Secondary
Time-weighted Summed Pain Intensity Difference (SPID) Over the 24-hour Study Period (SPID24).
The primary outcome measure is the summed pain intensity difference to baseline over the 24-hour study period (SPID-24). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 24 hour study period. The SPID-24 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The observed SPID-24 scores ranged from -70.00 to 148.70 in the active group to -58.09 to 160.24 in the placebo group. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity.
Time frame: 24 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | Time-weighted Summed Pain Intensity Difference (SPID) Over the 24-hour Study Period (SPID24). | 57.96 units on a scale | Standard Error 3.45 |
| Placebo Tablet | Time-weighted Summed Pain Intensity Difference (SPID) Over the 24-hour Study Period (SPID24). | 37.28 units on a scale | Standard Error 4.75 |
Secondary
TOTPAR12
Total pain relief over the 12 hours. The observed total pain relief scores ranged from 4.08 to 47.50 in the active group and 1.77 to 33.71 in the placebo group. A higher score indicates greater pain relief.
Time frame: 12 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | TOTPAR12 | 21.18 units on a scale | Standard Error 0.87 |
| Placebo Tablet | TOTPAR12 | 15.36 units on a scale | Standard Error 1.19 |
Secondary
TOTPAR24
Total pain relief over the 24 hour study period. The observed total pain relief scores ranged from 12.35 to 95.23 in the active group and 2.61 to 82.04 in the placebo group. A higher score indicates greater pain relief.
Time frame: 24 Hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Tablet 30 mcg | TOTPAR24 | 45.80 units on a scale | Standard Error 1.81 |
| Placebo Tablet | TOTPAR24 | 35.45 units on a scale | Standard Error 2.49 |